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Immunotherapy with OncoTherad® (MRB-CFI-1) associated with erythropoietin in the treatment of Ovarian Cancer: analyzes of the cytotoxic inflammatory response, immunological checkpoints and angiogenesis regulation

Grant number: 20/15687-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2021
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal researcher:Wagner José Fávaro
Grantee:Bianca Ribeiro de Souza Sasaki
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Among gynecological tumors, ovarian cancer (OC) is the most lethal and the most difficult to be diagnosed, being responsible for the highest mortality among cancers of the female reproductive system. Conventional chemotherapeutic drugs such as platinum/paclitaxel have toxic effects in addition to acquired resistance to the drug. OncoTherad® (MRB-CFI-1) is a nanostructured synthetic compound developed by our research group, which has antitumor and immunological properties reported in animals and humans through stimulation of the signaling pathway for interferon mediated by Toll-like receptors (TLRs) 2 and 4. Erythropoietin (EPO) has non-hematopoietic functions such as immunomodulation, anti-inflammatory, antioxidant and cytoprotective actions including in the female reproductive system. The tumoral microenvironment of CO involves a complex immunosuppressive network and the co-optation of pathways to check the immune system favors its establishment and evasion. Thus, the objective of the project is to characterize the histopathological and molecular effects of immunotherapy with OncoTherad® associated or not with the administration of EPO in the treatment of chemically induced CO in Fischer 344 rats. Therefore, the functioning of interrelated factors and signaling pathways implicated in ovarian carcinogenesis will be investigated, constituting a context of the profile of the inflammatory response in relation to the treatments: signaling pathway of Toll-like receptors (TLR2, TLR4, MyD88 and IRF-3); RANK / RANKL / OPG signaling pathway; immune checkpoints PD-1 / PDL-1 and CTLA-4; inflammatory response with markers of antitumor cytotoxic activity (IFN-³, iNOS and total F4 / 80 + macrophages) or pro tumor (IL-6, M2 CD163 + macrophages and Foxp3 + regulatory T lymphocytes); angiogenic activity with a pro angiogenic marker (VEGF), antiangiogenic (Endostatin) and quantification of blood capillaries (CD31). The combination of OncoTherad® and EPO can support the development of a new drug and thus another therapeutic alternative to CO. (AU)

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